Glycosylation pattern in cosmomycins is a distinctive feature among anthracyclines. These antitumor compounds possess two trisaccharide chains attached at C-7 and C-10, each of them with structural variability, mainly at the distal deoxysugar moieties. We have characterized a 14-kb chromosomal region from Streptomyces olindensis containing 13 genes involved in cosmomycin biosynthesis. Two of the genes, cosG and cosK, coding for glycosyltransferase were inactivated with the generation of five new derivatives. Structural elucidation of these compounds showed altered glycosylation patterns indicating the capability of both glycosyltransferases of transferring deoxysugars to both sides of the aglycone and the flexibility of CosK with respect to the deoxysugar donor. A model is proposed for the glycosylation steps during cosmomycins biosynthesis.
|Number of pages||10|
|Journal||Applied Microbiology and Biotechnology|
|State||Published - Nov 2006|
Bibliographical noteFunding Information:
Acknowledgements The authors thank specially collaborations of Drs. Arthur Gruber, Alda Madeira, Gilson P. Manfio, Valéria M. de Oliveira, and Hernando Del Portillo for the sequencing of the DNA, and the technical support of Dr. Fabiana Fantinatti-Garboggini, Dr. Emilio Fernando Merino, Karen Christina M. Simioni, and Daniele B. de Souza. This work was supported by grants from FAPESP to L.M.G. (00/07288-0) and to G.P. (03/00135-1), from the Spanish Ministry of Education and Science to L.M.G, R.L.A.F and C.M. (BMC2002-03599), and from the US National Institutes of Health (CA 091901 and CA 102102) to J.R. We thank Obra Social Cajastur for financial support to F.L.
ASJC Scopus subject areas
- Applied Microbiology and Biotechnology